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Combination cefixime/amoxicillin against penicillin-resistant Streptococcus pneumoniae infection
1Department of Infectious Diseases, Medicinal Biology Research Laboratories, Fujisawa Pharmaceutical Co., Ltd., Osaka, Japan.
Abstract:
The rising incidence of antibiotic resistance, including penicillin-resistant Streptococcus pneumoniae (PRSP), has become a great clinical problem in many countries. Cefixime, an orally active third-generation cephalosporin has broad and potent activity against various pathogens, especially gram-negative organisms including beta-lactamase producing strains. However, as with all other oral agents, cefixime is inactive against PRSP. As a possible solution to this problem, the effectiveness of a combination of cefixime and amoxicillin which retains stronger activity against PRSP was evaluated. This combination worked synergistically against S. pneumoniae including PRSP by the checkerboard method with a mean FIC index value of 0.60 and the time-kill kinetic method. Similarly, a synergistic effect was shown in the mouse respiratory tract infection model, with an FED index of 0.29 (cefixime:amoxicillin = 2:1). Additionally, this combination showed excellent activity against mixed organisms including PRSP, in the human serum level simulating kinetic method and mouse respiratory mixed infection models. We review here briefly preclinical studies carried out in our laboratory which demonstrate the synergistic effect of this cefixime plus amoxicillin combination, and suggest the empirical therapeutic potency of this combination for treating community-acquired respiratory tract infections, including PRSP, in the clinical setting.
Insights
A new cefixime and amoxicillin combination shows synergistic effects against penicillin-resistant Streptococcus pneumoniae (PRSP). This combination is effective for treating respiratory tract infections caused by PRSP.
Area of Science:
- Microbiology
- Pharmacology
- Infectious Diseases
Background:
- Antibiotic resistance, particularly penicillin-resistant Streptococcus pneumoniae (PRSP), poses a significant clinical challenge.
- Cefixime, a third-generation cephalosporin, is effective against many pathogens but inactive against PRSP.
- There is a need for effective treatments against PRSP infections.
Purpose of the Study:
- To evaluate the effectiveness of a combination of cefixime and amoxicillin against PRSP.
- To assess the synergistic activity of this combination in vitro and in vivo.
- To explore the potential of this combination for treating community-acquired respiratory tract infections.
Main Methods:
- Checkerboard method and time-kill kinetic assays were used to determine in vitro synergy.
- Mouse respiratory tract infection models were employed to evaluate in vivo efficacy.
- Human serum level simulating kinetic method was used to assess activity against mixed organisms.
Main Results:
- The cefixime-amoxicillin combination demonstrated synergistic activity against S. pneumoniae, including PRSP, with a mean FIC index of 0.60.
- In vivo studies showed a synergistic effect in a mouse respiratory tract infection model (FED index = 0.29).
- The combination exhibited excellent activity against mixed organisms, including PRSP, in simulated and in vivo models.
Conclusions:
- The cefixime-amoxicillin combination exhibits significant synergistic activity against PRSP.
- Preclinical studies suggest this combination has therapeutic potential for community-acquired respiratory tract infections.
- This combination may offer an effective empirical treatment option for infections involving PRSP.